Most human protein therapeutics require frequent dosing due to rapid clearance of the proteins from the body. Development of second generation protein pharmaceuticals that can be injected less frequently is of considerable interest to patients and healthcare providers. We propose to create long-acting forms of IL-11 and TPO by creating larger versions of these proteins with longer circulating half-lives. These modified IL-11 and TPO proteins will possess biological activities equal or superior to natural IL-I 1 and TPO in vivo, but will require less frequent dosing, on the order of once every one to three weeks, rather than daily. During Phase I we constructed IL-11 and TPO fusion proteins and demonstrated that certain of them possess near wild type in vitro bioactivities. We also demonstrated that one of the IL-11 fusion proteins has a significantly longer half-life than IL-11 in a rat. During Phase II, we will manufacture sufficient quantities of the modified proteins for more extensive pharmacokinetic and animal efficacy studies. The improved characteristics of the novel IL-11 and TPO proteins will reduce the amount of protein required per patient, improve patient compliance and quality of life and result in considerable cost savings to patients and healthcare providers. These proteins will find utility in treating thrombocytopenia resulting from cancer chemotherapy.